Construction of a Chiral Quaternary Carbon Center by Catalytic Asymmetric Alkylation of 2‑Arylcyclohexanones under Phase-Transfer Conditions

In this paper, we present an asymmetric alkylation of modified 2-arylcyclohexanones that employs a novel chiral ammonium bromide as a phase-transfer catalyst and an achiral auxiliary as a controller to improve the enantioselectivity to afford optically enriched products having a chiral quaternary carbon center

Metal-Free Enantioselective Hydroxyamination of Aldehydes with Nitrosocarbonyl Compounds Catalyzed by an Axially Chiral Amine

The first example of a highly regio- and enantioselective hydroxyamination of aldehydes with in situ generated nitrosocarbonyl compounds from hydroxamic acid derivatives was realized by combined use of TEMPO and BPO as the oxidant in the presence of a binaphthyl-modified amine catalyst

Practical Approach for Asymmetric Hydroxyamination of Aldehydes with <i>in Situ</i> Generated Nitrosocarbonyl Compounds: Application to One-Pot Synthesis of Chiral Allylamines

The highly regio- and enantioselective hydroxyamination of aldehydes with <i>in situ</i> generated nitrosocarbonyl compounds from a hydroxamic acid derivative was realized by simple and readily available chiral amine catalysts. The resulting hydroxyamination products were readily converted to the corresponding chiral 1,2-aminoalcohol or allylamine derivatives in one pot

Synthesis of <i>N</i>‑Boc-Propargylic and Allylic Amines by Reaction of Organomagnesium Reagents with <i>N</i>‑Boc-Aminals and Their Oxidation to <i>N</i>‑Boc-Ketimines

Previously inaccessible <i>N</i>-Boc-protected propargylic and allylic amines were synthesized by the reaction between <i>N</i>-Boc-aminals and organomagnesium reagents through the in situ generated <i>N</i>-Boc-imine intermediates. The obtained <i>N</i>-Boc-propargylic amines could be readily converted into unprecedented <i>N</i>-Boc-ketimines by oxidation with manganese dioxide

Amine-Catalyzed Asymmetric Cross-Aldol Reactions Using Heterofunctionalized Acetaldehydes as Nucleophiles

Various heterofunctionalized acetaldehydes were successfully employed in an amine-catalyzed asymmetric cross-aldol reaction, affording a variety of synthetically useful 1,2-difunctionalized compounds such as 1,2-diols and 1,2-aminoalcohols. With this method, both <i>syn</i>- and <i>anti</i>-1,2-difunctionalized compounds were obtained from the same set of reactants by using the appropriate amine catalyst

Powerful Amino Diol Catalyst for Effecting the Direct Asymmetric Conjugate Addition of Aldehydes to Acrylates

Di-<i>tert</i>-butyl methylenemalonate (<b>1</b>) could be employed as a reactive equivalent of a three-carbon Michael acceptor such as acrylate in a direct asymmetric conjugate addition of aldehydes catalyzed by an axially chiral amino diol (<i>S</i>)-<b>3a</b>. Furthermore, acrylate, an unexplored and challenging substrate in enamine catalysis, has also been successfully employed in asymmetric conjugate addition reaction. Relatively inert acrylate is doubly activated by polyfluoroalkyl group of <b>2</b> and the hydroxyl group on the axially chiral amino diol catalyst (<i>S</i>)-<b>3b</b>, giving corresponding conjugate adducts in high yield with excellent enantiomeric excess. The obtained conjugate addition products were readily converted to synthetically useful and important chiral building blocks

Powerful Amino Diol Catalyst for Effecting the Direct Asymmetric Conjugate Addition of Aldehydes to Acrylates

Di-<i>tert</i>-butyl methylenemalonate (<b>1</b>) could be employed as a reactive equivalent of a three-carbon Michael acceptor such as acrylate in a direct asymmetric conjugate addition of aldehydes catalyzed by an axially chiral amino diol (<i>S</i>)-<b>3a</b>. Furthermore, acrylate, an unexplored and challenging substrate in enamine catalysis, has also been successfully employed in asymmetric conjugate addition reaction. Relatively inert acrylate is doubly activated by polyfluoroalkyl group of <b>2</b> and the hydroxyl group on the axially chiral amino diol catalyst (<i>S</i>)-<b>3b</b>, giving corresponding conjugate adducts in high yield with excellent enantiomeric excess. The obtained conjugate addition products were readily converted to synthetically useful and important chiral building blocks

Synthesis of 3‑Mono-Substituted Binaphthyl-Based Secondary Amine Catalysts via Monobromination of an Axially Chiral Dicarboxylic Acid Derivative

A facile synthetic route to a 3-bromo binaphthyl-based secondary amine through the monobromination of an axially chiral dicarboxylic acid derivative has been developed. The combination of this new procedure with coupling reactions established an efficient synthetic approach to a series of binaphthyl-based secondary amine catalysts containing various functional groups in an efficient way

Stereocontrolled Synthesis of Vicinal Diamines by Organocatalytic Asymmetric Mannich Reaction of <i>N</i>-Protected Aminoacetaldehydes: Formal Synthesis of (−)-Agelastatin A

The 1,2-diamine (vicinal diamine) motif is present in a number of natural products with interesting biological activity and in many chiral molecular catalysts. The efficient and stereocontrolled synthesis of enantioenriched vicinal diamines is still a challenge to modern chemical methodology. We report here both <i>syn</i>- and <i>anti</i>-selective asymmetric direct Mannich reactions of <i>N</i>-protected aminoacetaldehydes with <i>N</i>-Boc-protected imines catalyzed by proline and the axially chiral amino sulfonamide (<i>S</i>)-<b>3</b>. This organocatalytic process represents the first example of a Mannich reaction using Z- or Boc-protected aminoacetaldehyde as a new entry of α-nitrogen functionalized aldehyde nucleophile in enamine catalysis. The obtained optically active vicinal diamines are useful chiral synthons as exemplified by the formal synthesis of (−)-agelastatin A

Stereocontrolled Synthesis of Vicinal Diamines by Organocatalytic Asymmetric Mannich Reaction of <i>N</i>-Protected Aminoacetaldehydes: Formal Synthesis of (−)-Agelastatin A

The 1,2-diamine (vicinal diamine) motif is present in a number of natural products with interesting biological activity and in many chiral molecular catalysts. The efficient and stereocontrolled synthesis of enantioenriched vicinal diamines is still a challenge to modern chemical methodology. We report here both <i>syn</i>- and <i>anti</i>-selective asymmetric direct Mannich reactions of <i>N</i>-protected aminoacetaldehydes with <i>N</i>-Boc-protected imines catalyzed by proline and the axially chiral amino sulfonamide (<i>S</i>)-<b>3</b>. This organocatalytic process represents the first example of a Mannich reaction using Z- or Boc-protected aminoacetaldehyde as a new entry of α-nitrogen functionalized aldehyde nucleophile in enamine catalysis. The obtained optically active vicinal diamines are useful chiral synthons as exemplified by the formal synthesis of (−)-agelastatin A